Indian Institute of Public Health Gandhinagar, India

^*Corresponding author: Sirwani B, Indian Institute of Public Health Gandhi nagar (IIPHG), Gujarat-382042, India; Email: barkhasirwani866@gmail.com

Copyright: © 2021 Sirwani B, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Acute malnutrition in infants under six months (u6m) is increasingly recognized as a serious public health concern, as the evidence from developing countries suggests that acute malnutrition affects around 8.5 million u6m infants. Despite this, the current evidence base on the management of acute malnutrition in under six months infants is sparse. The objectives of this paper were to present the burden and underlying risk factors associated with acute malnutrition and synthesize current evidence on various assessment and management approaches currently in use for infants u6m.

Methods: Two electronic databases, PubMed and Cochrane Library were searched between April 2020 and May 2020. We systematically reviewed the literature and identified 33 papers that fulfilled the inclusion and exclusion criteria. Results: One third of the identified studies (n=10, 30.3%) were secondary data analysis. The studies were geographically diverse (LICs + LMICs), of which six were multi-country studies. The review identified that South Asian countries bear the highest burden of acute malnutrition in u6m infants. In order to identify the u6m infants at the risk of mortality, severe underweight at 6 weeks of age could be a potential indicator (requires further evidence from different contexts). Majority of the studies identified maternal related factors to be mainly associated with acute malnutrition in u6m infants. Among preventive interventions, one with maternal nutritional supplementation (MNS) in addition to breastfeeding support showed promising improvement in anthropometric outcomes.

Conclusion: Health programmes, particularly in South Asia region require to focus on maternal related factors to avert and/or manage growth faltering in u6m infants. Further research on context specific burden of acute malnutrition and identification of underlying risk factors, is urgently required for shaping new programs and/ or for incorporating u6m in the existing malnutrition management programs.

Assessment; Management; Acute malnutrition; Wasting; Infants under six months

Childhood malnutrition is a global public health problem and it is known that majority of the children become susceptible to malnutrition during periods of vulnerability i.e., during the intrauterine period and the early years of life [1]. Wasting (acute malnutrition or wasting have been used interchangeably) in infants under six months (u6m) is increasingly recognized as a serious public health concern [2]. Evidence from developing countries reveal, an estimated 8.5 million infants aged u6m being wasted [3], of which nearly 4.7 million infants aged u6m being moderately wasted, and approximately 3.8 million as severely wasted [4]. These wasted u6m infants constitute an important proportion of all wasted children aged less than five (< 5) years [5]. More than half of all wasted < 5 children in the world live in southern Asia [6], and the age distribution of wasting in this region reveals that the highest prevalence is seen at birth and most of the infants experience their first wasting episode by three months of age [7,8].

When compared to the older children-the physiological processes, including thermoregulation, renal and gastrointestinal functions, are relatively immature in infants u6m [9], Infants are more susceptible to frequent and severe infections as their immune systems are still developing [1], they are less able to make their needs known and are more vulnerable to the effects of poor parenting [10], diagnosing oedema in infants might be more challenging, as most of the older children can stand, and gravity might influence in narrowing the location of the oedema to the limbs in the older children and also, evidence suggests that infants u6m face higher mortality risk during treatment of acute malnutrition [11].

There are several risk factors associated with wasting infants u6m. Some studies have broadly categorized these risk factors into infant related, maternal-related, and household-related factors [7,12]. Most commonly, severe acute malnutrition in this age group is known to occur due to suboptimal feeding practices, especially breastfeeding practices [9,13]. As per WHO recommendations, infants u6m should be exclusively breastfed however [14], in low-income and lower-middle income countries (LICs and LMICs), only 37% of children younger than 6 months of age are exclusively breastfed [15]. Studies have shown that even exclusively breastfed infants are susceptible to acute malnutrition [16,17].

Assessment of infants u6m is an essential step to identify acutely malnourished infants and accordingly enroll them into nutrition programmes. However, authors have reported that infants u6m are often excluded from nutrition surveys and marginalized in nutrition programmes [12]. The two anthropometric indicators commonly used for assessing severe acute malnutrition (SAM) in children aged 6-59 months are also being considered for infants u6m [9], namely weight-for-height z score (WHZ) and mid-upper arm circumference (MUAC). However, in order to compute WHZ, length/ height is required, which is especially difficult to measure in younger infants (u6m infants) [18]. Further, there are no standards for calculating weight-for-height (WFH) for those with length <45 cm [19].

It is challenging to manage malnutrition in u6m infants as it is complex and multifactorial [12,19]. Thus, in 2013, for the first time WHO guidelines on the management of SAM recognized u6m as a special group and included a chapter dedicated to the management of infants u6m [9]. Facility-based management of these infants include the use of F-75 or diluted F-100 milk via a supplementary suckling technique until exclusive breastfeeding is re-established with/without antibiotic therapy during the stabilization phase [20]. Focusing only on facility-based strategies might lead to increased admissions, which might have serious implications on resources [21]. Hence, WHO mentions community-based management approach for uncomplicated cases/at-risk infants. Findings from a qualitative study in Senegal showed that community-based care for uncomplicated cases of acute malnutrition in infants u6m improved their access to care [22].

With paucity of evidence on actual burden and associated risk factors, also, with uncertainty in assessment and management approaches, it is difficult to design specific programs focusing on u6m infants. Through this review, we aim- to present the estimated the burden of acute malnutrition in u6m infants and also explore and synthesize evidence on various assessment and treatment approaches used for infants u6m.

- To explore and synthesize evidence on various assessment and treatment approaches used for infants u6m.
- To identify the current evidence on burden of acute malnutrition in infants u6m.
- To explore and identify underlying risk factors associated with acute malnutrition in infants u6m.

The methods for this review follow the criteria of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta- Analyses) statement [23].

The literature search was conducted on two electronic databases- PubMed and Cochrane Library. At the initial stage filter for language (English), species (Human), age (Infant: birth-23 months, Infant: 1-23 months, Newborn: birth-1 month) and publication date (2000- 2020) were applied in PubMed database. For PubMed database both ‘controlled vocabulary’ and ‘free-text’ terms were used. Similar search terms were applied for both the databases, according to databases’ advanced search set-up. The final search strategy was run on 15th May, 2020.

Search Strategy: ((((“Infants”[Text Word] OR (“under”[All Fields] AND “six months”[Text Word])) OR ((((“infant”[MeSH Terms] OR “infant”[All Fields]) OR “Infants”[All Fields]) OR “infant s”[All Fields]) AND “under 6 months”[Text Word])) OR ((((“infant”[MeSH Terms] OR “infant”[All Fields]) OR “Infants”[All Fields]) OR “infants”[All Fields]) AND “aged 6 months”[Text Word])) AND (((((((((((((“management”[Text Word] OR “admission”[Text Word]) OR “admission profile”[Text Word]) OR “Discharge”[Text Word]) OR “discharge outcome”[Text Word]) OR “outcome”[Text Word]) OR “diagnostic criteria”[Text Word]) OR “prevalence”[Text Word]) OR “risk factor”[Text Word]) OR “support”[Text Word]) OR “breastfeeding support”[Text Word]) OR “F-100”[Text Word]) OR “diluted f-100”[Text Word]) OR “infant formula”[Text Word])) AND (((((((((((“severe acute malnutrition”[Text Word] OR “sam”[Text Word]) OR “severe malnutrition”[Text Word]) OR “acute malnutrition”[Text Word]) OR “wasting”[Text Word]) OR “wasted”[Text Word]) OR “MUAC”[Text Word]) OR “weight for age”[Text Word]) OR “WAZ”[Text Word]) OR “weight for height”[Text Word]) OR “WHZ”[Text Word]) OR “Anthropometry”[Text Word]).

Screening: The selection of the studies was performed using two stage selection process using explicit inclusion and exclusion criteriafirst based on title and abstract and later based on full-text. It was performed in EPPI-Reviewer software (version: 4.11.1.1) [24].

- Population: Infants u6m of age (Low birth weight infant, preterm infants, small for gestational age were included)
- Intervention(s)/Exposure(s): risk factor, diagnostic criteria, admission/ discharge criteria, formula feeding, F-100/ diluted F-100, counselling of mothers of u6m infants (prenatal as well as postnatal), postnatal interventions on mothers of u6m infants.
- Comparator: Any
- Outcome: any of the following- Weight-for-age (WAZ), Weight-for-height (WHZ), Mid Upper Arm Circumference (MUAC), morbidity, mortality due to malnutrition.
- Context: Studies with a focus on LIC or LMIC, based on World Bank classification of country on income group, 2019 (in case of multi-country study, at least one country belongs to LIC/LMIC group) [25].
- Study design: observational, interventional and secondary data analysis studies

Exclusion Criteria: We excluded the articles that were qualitative, systematic reviews, trial protocols, case studies, or published in abstract form only. Articles, where the evaluation was done for congenital abnormalities, diseases, illness, hospitalization for reason other than malnutrition or HIV-exposed population was excluded. Articles with prime focus on overweight/obesity or stunting (chronic malnutrition) were also excluded.

The extracted data included characteristics of the study population, brief description of-intervention (s)/ exposure (s), comparator if present in the study, outcome and context.

Quality assessment was performed for all the studies except for studies with secondary data analysis study design. Two checklists were used- for interventional studies, quality was assessed using ‘Methods for the development of National Institute for Health and Care Excellence (NICE) public health guidance’ [26], and for observational studies, the quality was assessed using- ‘Quality assessment tool for observational cohort and cross-sectional studies and, quality assessment tool for case-control studies by National Institute of Health, National Heart, Lung, and Blood Institute (NIH, NHLBI)’ [27].

The analysis is presented in the form of a narrative synthesis. However, where the authors had stated significance of the finding, it is presented in the results table as P-values. The evidence is presented as- (percentage/mean/ratio/median) for the u6m population as one group or as a comparison between the intervention group (IG) and the control group (CG). Since this review involves a variety of interventions/exposures, this led to a methodological heterogeneity in the results. Thus, final results are presented under categories/ clusters, formed based on the type of intervention/exposure identified in the included studies.

The review protocol was submitted to the ethical committee at the Indian Institute of Public Health, Gandhinagar (IIPHG). The protocol was assessed by research ethics committee and an exemption was granted.

Initial search identified 3,689 articles. Of these, 440 articles were removed as duplicates, the remaining 3,249 records were screened in stage-1. The screening based on title and abstract lead to exclusion of another 3,177 records. Remaining 72 records were included in stage-2 for full text assessment. Of these, 39 were excluded based on predetermined inclusion and exclusion criteria. Finally, 33 records were included for analysis (Figure 1).

Characteristics of the included studies are presented in Table 1. Among the included studies, one-third of the studies were secondary data analysis (SDA) followed by seven randomized controlled trials (RCTs) seven prospective cohort studies (PCS) [3,11,13,16,18,28-46] (Table 1). Six studies were multi-country studies [3,11,18,30,32,36], followed by six studies from India [16,31,35,40,47,48] and three from each of these countries-Uganda [29,46,49], Bangladesh [38,42,43], Pakistan [39,45,50], Kenya [28,34,51].

Interventions and Outcomes: Of 33 studies, 12 (36.4%) studies observed both prevalence and risk factors, seven (21.2%) studies focused on prevalence, six (18.1%) assessed preventive interventions, four (12.1%) focused on treatment of wasting and three (9.1%) assessed risk factors associated with malnutrition (Table 1). One (3%) study focused on the assessment i.e., indicators used to assess acute malnutrition and predicting mortality in malnourished infants.

Of the total studies, anthropometry outcome was measured in 30 studies (90.9%), morbidity outcome in six studies (18.1%), mortality was observed in six studies (18.1%) and discharge outcomes in three studies (9.1%) (Table 1).

Effect of Interventions on Specific Outcomes: Anthropometry Outcomes: Of total 30 studies reporting outcomes on anthropometry, 26 reported WAZ and 21 reported WHZ. Of these, 12 focused on both prevalence and risk factors, seven focused on prevalence, six on preventive interventions and two on treatment aspect of acute malnutrition in u6m infants (Table 2).

Effect of intervention/Exposure on outcome (for details of each study refer Table 2).

Prevalence (WHZ): Of the total 21 studies reporting WHZ, 15 studies presented prevalence of wasting in infants u6m. Of these, 11 considered prevalence based on WHO growth standards, two considered prevalence based on National Center for Health Statistics (NCHS) growth standards, while two studies compared prevalence based on both the standards. Prevalence of wasting was measured at different ages/ time points in different studies, however, all the studies measured prevalence among infants ≤ 6 months.

Figure 2 presents prevalence reported as per WHO/ NCHS growth standards in the studies, except one study that reported mean WHZ score [49], Which is not presented in this figure. As per WHO growth standards, highest prevalence of wasting was observed in an India based study- 30.6% infants u6m reported as wasted [16]. Lowest prevalence was reported as 2% in Uganda [46]. As per NCHS standards, highest prevalence was reported as 6.7% by a multicountry study [18]. Lowest prevalence was reported as 0% in Malawi [41] (Figure 2). While severe wasting was reported by Nigeria based case-control study- among all the cases of 0-3 months infants with undernutrition, 22.9% (0-3 mo) infants were reported to be severely wasted [55].

Prevalence (WAZ): Of the total studies, 17 had reported underweight prevalence. Of which, 13 studies measured prevalence of underweight based on WHO growth standards, three studies measured underweight based on NCHS standards and one study reported prevalence based on both the standards. Prevalence of underweight was measured at different ages/time points in different studies, however, all the studies measured prevalence among infants ≤ 6 months of all the studies reporting underweight prevalence, a Zambia based study reported prevalence in the form of range (19- 28% as per WHO standards and 3-15% as per NCHS) and another Uganda based cross-sectional study reported mean WAZ score (-0.41) [49,53]. Results of remaining 14 studies are shown in Figure 3 - as per WHO standards, highest prevalence of underweight was observed in two studies, one was India based study and another was Pakistan based study [40,50]. A case-control study conducted in Nigeria reported very high prevalence (%) of severe underweight among cases of 0-3 months infants with undernutrition(55)Risk factors (WAZ / WHZ) (for details of each study refer Table 2): Of the total 15 studies focused on risk factors, 13 studies reported factors associated with WAZ/ underweight and nine studies reported factors associated with WHZ/ wasting in infants u6m. Various risk factors identified from these studies are presented below:
• Maternal BMI: Two studies reported maternal BMI [18,28] as a significant factor correlated (Spearman rank correlation coefficient, r=0.78) [26] /associated with underweight/ WHZ in infants u6m (P< 0.05) [28].
• Maternal depression: Three studies reported maternal depression as a factor associated with infant’s underweight.
Two studies found significant association of maternal depression with underweight in infants u6m [45,51]. Rahman et al. (OR 3.5; 95% CI: 1.5-8.6; P<0.01) [45], and Madeghe et al. (adjusted odds ratio- AOR 5.79; 95% CI: 2.14 –15.62; P = 0.001) [51], however one study focused on both prenatal as well as postnatal depression and other study reported only postpartum depression [45,51]. On the other hand, Nasreen et al. found non-significant association of maternal depressive symptoms (during pregnancy and 2-3 mo postpartum) with infant’s underweight at 2-3 mo [43].

Place of Delivery: Two studies (Nigeria-based) found a place of delivery as a factor significantly associated with underweight or wasting in infants u6m [54,55]. Of these two studies, one was a case-control, which found that infants delivered at residential homes compared with the public hospitals had almost threefold odds of being severely underweight (AOR 2.98; 95% CI: 1.51–5.88; P= 0.002) or severely wasted (AOR 2.90; 95% CI: 1.32–6.37; P = 0.008), when controlled for potential confounders [55]. The other study which was cross-sectional in nature reported infants born out of hospital had higher odds of being underweight (OR 1.27; 95% CI: 1.08, 1.49; P=0.004) or wasted (OR 1.44; 95% CI: 1.20, 1.73; P<0.001) compared to those born at hospitals [54].

Socioeconomic Status: Three studies observed association of indicators related to socioeconomic status of the family with underweight or wasting in infants u6m [29,45,50]. The Uganda based study performed secondary data analysis to see socioeconomic distribution of underweight or wasting, and found that prevalence of underweight (at 24 wks: concentration index -0.226, at 12 wks: concentration index -0.301) or wasting (at 24 wks: concentration index -0.253, at 12 wks: concentration index -0.213) was significantly concentrated among poor [29]. Another study from Pakistan, reported family income as a factor associated with underweight and found that higher proportion of infants from low income families were underweight when compared to infants in moderate income families (OR 1.15, 95% CI: 1.03-1.29, P = 0.017) [50]. Rahman et al found relative poverty as a factor significantly associated with underweight (OR 2.3; 95% CI: 1.1-5.2; P< 0.05) in infants u6m [45].

Maternal Factors: Maternal haemoglobin concentration and mother’s education status were significantly and positively associated with underweight. Mother’s periodontal health was significantly associated with infant’s WHZ. Factors like maternal autonomy [28,54,46,47], mother’s childbearing age and having multiple pregnancies were significantly associated with underweight or wasting in infants u6m. While, association of restricted maternal diets, during postpartum period with infant’s underweight or wasting was found to be negative, but insignificant [52,54].

Infant Related Factors: An India based study found that nasopharyngeal carriage of streptococcus Pneumococci (spn) in infants (at 2 mo) was significantly associated with WAZ score but not with WHZ (at 6 mo) [40]. Another study reported that infant’s gender (i.e. when compare to female, male infants had higher odds of being underweight- OR 1.31, 95% CI 1.21, 1.54, P=0.001 or wasted- OR 1.26, 95% CI 1.05, 1.50, P=0.011, adjusting for covariates) and this association was found to be significant, however history of hyperbilirubinemia was associated with underweight only [54]. Two studies observed infant’s morbidity status as a risk factor [28,45]. Of these, one study reported that ≥ 5 diarrhoeal episodes per year was significantly associated with underweight [45], while the other reported no significant association of infant’s morbidity index with underweight [28].

Household Factors: A Bangladesh based longitudinal study observed association of household (HH) arsenic exposure on infant’s underweight or wasting, but found it to be insignificant [42]. Another study reported, living in rented accommodation vs owned was associated with a lower risk of infant being underweight (OR 0.64; 95% CI: 0.45, 0.90; P=0.011) or wasted (OR 0.45; 95% CI: 0.31, 0.65; P<0.001) [54].

Preventive Intervention (WAZ): All the six studies with focus on preventive intervention reported anthropometric outcomes. Of these, five studies reported WAZ/ underweight [33,36,37,39,48] (for details of each study refer Table 2). Of these five studies, two were communitybased studies, where counseling on EBF was given through home visits. However, one study had peer counselors selected from the same village [36], while the other one had two intervention groups with breastfeeding (BF) counselors or childcare (CC) counselors [33]. At end of the trial both the studies found only small changes in WAZ scores of IG vs CG, which were non-significant [33,36]. A prospective cohort assessment was conducted in India to evaluate a program that in addition to government services, involved age specific recommendation of BF and CF in the intervention arm. The results showed that the proportion of underweight in IG (37.2%) was lower than CG (44.4%), but this difference was insignificant [48]. On other hand, Vietnam based RCT in conjunction with a breastfeeding support program also used maternal nutritional supplementation (MNS) in the intervention arm and at the end of the trial, trends for WAZ score development over time (birth to 12 weeks postpartum, estimate 0.16; 95% CI: -0.03, 0.36, P=0.0636) were significantly higher in the intervention group [37]. Only one study had the intervention focused on mothers with depression, which involved home-based cognitive behavior therapy sessions in the intervention arm, at the end of the trial differences in infant’s WAZ score (adjusted mean difference - 0.02; 95% CI: −0.18 to 0.14, P=0.76) was non-significant [39].

Preventive Intervention (WHZ): Of six studies, only two reported WHZ/wasting [35,36]. Both the studies had communitybased counselling of EBF as intervention. Of the two, an India based study found that prevalence of wasting in IG vs CG was 3% vs 3% and for LBW infants it was 3% vs 5%, with this difference being nonsignificant [35]. The other study was a multi-country trial, which showed the differences in wasting prevalence ratios between two groups were small and non-significant in Burkina Faso and South Africa, while in Uganda prevalence of wasting in IG vs CG was 7.56% vs 3.16%, and was significant [36].

Treatment (WAZ / WHZ): Of the four studies focusing on treatment aspect, only two had reported anthropometry outcomes [11,38]. First was a study on the dietary management in the rehabilitation phase of SAM in infants u6m, which described three interventions F-100, diluted F-100 (F-100D), and Infant Formula (IF). Positive impacts on WAZ scores and WLZ scores in all the three groups were reported at the end of the trial, but significance of these changes was not reported [38]. However, duration of recovery was reported to be significantly better with F-100D (median duration in days: F-100 vs Diluted F-100 -1.9, 95% CI -3.9 to 0.2, P=0.07; F-100 vs IF: - 3.3, 95% CI -5.7 to -0.9, P=0.008; Diluted F-100 vs IF: -1.4, 95% CI - 3.8 to 1.1, P=0.26) [38]. The other study was on inpatient therapeutic care program for acute malnutrition, which reported 85.0% infants u6m being wasted at admission, of which 14.5% were moderately wasted and 70.6% were severely wasted and mean WHZ score for infants u6m was -3.89 [11].

Morbidity outcome(s): Of total six studies reporting morbidity outcomes, three were prevalence studies [13,44], Two studies focused on preventive intervention [33,35], and one study focused on treatment component of acute malnutrition/ wasting in infants u6m [31] (Table 1).

Effect of intervention/Exposure on outcome (for details of each study refer Table 2).

Prevalence: Three studies that reported morbidity prevalence in infants u6m are shown in Figure 4. Highest prevalence of diarrhea was reported by India based SDA [16], while highest prevalence of fever was reported by a SDA performed in Ethiopia and highest prevalence of ARI symptoms was reported by a study conducted in Indonesia [13,,44].

Preventive intervention: Both the studies assessed community-based counseling on EBF as an intervention and no specific intervention was provided to the control group. One was Philippines based RCT that reported IG2: childcare group and CG: control groups had higher rates of diarrhea (IG2=28.3% and CG=30.5%) than the IG1: breastfeeding counselled group (IG1=15%) [33]. The other study was India based RCT, which reported prevalence of diarrhea at 6 months in IG vs CG was (25% vs 28%), i.e., significantly lower in intervention group (P=0.04) [35].

Treatment: One study observed admission profile of infants u6m with SAM admitted in Nutrition rehabilitation center (NRC) in India, and reported- at admission most common symptom that the infants presented with, was acute diarrhoea [31] (Figure 4).

Mortality outcome(s): Of the six studies reporting mortality outcome, four focused on treatment [11,31,34,38]. Among remaining two, one was based on preventive intervention [33], and other on assessment aspect [32] (Table 1).

Effect of intervention/Exposure on outcome (for details of each study refer Table 2).

Treatment: Among the four studies, two studies were SDA [11,31], one was India based study, that analysed data to see discharge outcomes of 108 infants with SAM admitted in NRC and reported death of 3 infants [31]. Other study was based on data from 10 countries and reported death of (4.60%) infants u6m before discharge, also infants u6m were found to have a greater risk of mortality (risk ratio 1.30, P< 0.01) during treatment, when compared to older children [11]. Mortality in IG vs CG was reported by two RCTs [34,38]. One RCT with intervention- daily co-trimoxazole prophylaxis given to children without HIV being treated for complicated SAM, reported (21.62% vs 27.21%) 2-5 months old infant deaths in IG vs CG [34]. Other study, compared three diets for dietary management in the rehabilitation phase of SAM in infants u6m- Group1: F-100, Group2: F100D and Group3: IF, and death at the end of trial was reported in F-100 group only (2%) [38].

Assessment: A multi-country study, determined the sensitivity and specificity of nutritional status indicators for predicting death during infancy and reported that- at 6 weeks of age, underweight or wasting in India was associated with an increased risk of death before 6 months of age, while no indicator was a good predictor of mortality at 6 months age in Ghana or Peru [32].

Discharge outcome(s): Of the four studies that focused on treatment, three reported discharge outcomes [11,31,38]. A study with three IGs (F-100 vs F-100D vs IF) reported duration of recovery i.e., infants who received F-100 recovered more quickly than infants who received infant formula (P = 0.016) but not more quickly than infants who received diluted F-100 (P =0.09) [38]. Another study reported percentage of infants admitted in NRC that were cured i.e., 69.4%, while percentage of infants u6m non-recovered were 26.8% [31]. Of those cured, 42.6% were cured using supplementary suckling technique (SST), 30.6% cured using F-100D and 26.6% cured with correction of positioning and attachment only [31]. The study based on SDA of datasets on inpatient therapeutic care programme for acute malnutrition from 10 countries reported- 75.7% infants as recovered, while 10.2% as non-recovered [11] (refer Table 2 for details).

The review included 33 studies that were focused on different aspects related to acute malnutrition in u6m infants. These studies had varied methodology and were from different countries belonging to LICs or LMICs [25]. Majority (n=22) of the included studies focused on prevalence and risk factors associated with acute malnutrition. However, the target population was diverse in these studies, with some having sole focus on u6m infants while others incorporating sub group analysis for this age group.

Only one study focusing on assessment of u6m infants with acute malnutrition met the inclusion criteria. The study reported that, to identify infants at higher risk of mortality at 6 months age, severe underweight at 6 weeks age (i.e., age of routine immunization) could be considered as better indicator when compared to low WLZ score [32]. Similar findings were reported by Lelijveld N et al., in a review of methods to detect cases of severely malnourished infants u6m, the author rated WFA, MUAC as indicators over WLZ, for acute malnutrition and associated mortality in infants u6m [56]. The probable explanation for this could be the fact the WLZ has poor predictive value or low sensitivity to predict infant’s death and many WLZ values are incalculable using current WHO growth standards [56,57,58]. WHO’s current recommendations for u6m infants adopted the same criteria used for older children (i.e., use of WLZ for identifying mortality risk), however these recommendations were made in absence of quality evidence and recently emerging evidence has reported WLZ as poor indicator for u6m infants [9].

Four studies focusing on the treatment aspect were identified in this review [11,31,34,38]. The included studies found that u6m infants had a higher risk of mortality during treatment compared to the older children. However, u6m infants showed less default rate than the older children at discharge [11,34]. The higher vulnerability of these u6m infants could be one of the reasons explaining their higher mortality rate, when compared to older children (6- 59 months age).

In the study by Singh et al., majority of the inpatient infants were treated by simple interventions like- counselling, SST, correction of breast positioning and attachment [31]. These findings suggest that simple interventions could be easily incorporated in outpatient programs and a considerable case load of u6m could be managed in community itself, reserving the inpatient admissions for complicated cases (cases with oedema and danger signs).

For inpatient management of u6m infants with SAM, WHO guidelines based on earlier evidence stated F-100 to be unsafe for u6m infants with SAM, owing to high renal solute load and risk of hypernatraemic dehydration [9]. However, recent evidence from a study conducted by Islam et al., suggested that for infants who are gaining weight rapidly in a hospital environment with well-controlled preparation of feeds, F-100 is safe and that there is no need to prepare an alternative type of feed for infants u6m [38]. These contrasting findings highlight the need of further research in this field to generate concrete evidence.

The review also explored postnatal/ postpartum interventions that prevent growth faltering in u6m infants. Studies (n=4) mainly involved community-based promotion of breastfeeding practices as the intervention [33,35,36,48]. These interventions successfully improved breastfeeding practices in the intervention group and two studies, reported significantly less diarrhea prevalence in IG [33,35]. However, this improvement was not translated to infant’s anthropometric outcomes at 6 months. This review observed outcomes at 6 months only. Thus, it is possible that improvement in anthropometry might have occurred, when follow up was carried out at later ages.

A study by Huynh et al, incorporated MNS in the intervention, in conjugation with BF support. This intervention reported significant trends for higher WAZ score development over time (birth to 12 weeks postpartum) in the infants of IG [37]. This finding explains the importance of incorporating mother’s nutritional component in the interventions addressing the prevention of growth faltering in u6m infants.

Another study that offered cognitive behavioral therapy (counseling sessions) for mothers with depression presented no significant differences in underweight prevalence between IG vs CG, but other significant benefits of this intervention were reported [39].

Risk factors associated with acute malnutrition in u6m infants were reported by (n=15) studies in this review. The factors that were reported as significant were grouped into three categories- maternal related, infant related and HH/ sociodemographic related. Majority of the studies reported maternal related factors. Factors like maternal autonomy, mother’s childbearing age, place of delivery, and parity were significantly associated with either underweight or wasting. While, maternal BMI, mother’s mental health (depression), maternal education, maternal hemoglobin concentration were factors significantly associated with infant’s underweight/WAZ score. On the other hand, mother’s periodontal health (low CPI score) was found as a significant risk factor associated with infant wasting/WHZ score.

A systematic review by G.J. Carlson et al., reported similar findings in terms of, positive association between maternal autonomy and child’s nutritional indicators in developing countries [59]. This review considered broad age group of children (0-60 months age) as target population, however there were studies that incorporated u6m infants as well.

The review also identified many infant-related risk factors, like infant’s gender and chronological age, which were found to be significant risk factors associated with both underweight or wasting. While, nasopharyngeal carriage of pneumococci (spn) in infants at 2 mo age, history of hyperbilirubinemia, ≥5 diarrhoeal episodes per year, were the risk factors significantly associated with underweight/ WAZ score. In addition, acute malnutrition in u6m infants was more concentrated among poor and low-income families.

Some factors that were reported as non-significant by the authors were- HH arsenic exposure, maternal restricted diets in pospartim period, number of siblings, maternal and infant’s morbidity index, and others. However for HH arsenic exposure, author reported no association of HH arsenic exposure with underweight or wasting but found association with stunting, indicating a chronic long term effect of HH arsenic exposure [42].

This review also identified burden of acute malnutrition in u6m infants. Studies reporting the prevalence of wasting and underweight were from three regions according to World Bank classification, i.e., South Asia, Sub-Saharan Africa, and East Asia & Pacific [25]. The highest prevalence of both wasting and underweight as per WHO growth standards was found in the South Asia region. With 30.6% and 30.0%, two India based studies reported the highest wasting prevalence followed by Bangladesh with 23.3% [16,30,42], with both the countries falling in a critical situation as per WHO cut-off values for public health significance. Similar findings were reported in a oneday consultation organized by UNICEF on wasting in South Asia, which reported that more than one in three children in India have wasting (WHZ <-2 SD) during the first three months after birth [8]. When looking at underweight prevalence found in this review, as per WHO cut-offs, very high underweight prevalence was reported from both India and Pakistan (37.4%), followed by Kenya (34%), and high prevalence was reported from Bangladesh based study (23% to 25%).

The findings of this review should be interpreted with the following limitations. For screening based on title & abstract, studies where age group was not mentioned or had a broader age group (<1, <2, <5 years or <11, <23 months, etc.), inclusion for full-text screening was considered if sub-group analysis was mentioned in the abstract or based on the reviewer’s judgment. During the initial search some filters were applied in the search strategy, this could have led to a bias in the total number of records found initially. Due to the broad scope of this review, there was considerable heterogeneity in the interventions and outcomes. A large number of studies were included based on the full text; hence details of individual studies could not be discussed. A qualitative tool was used for quality appraisal, which could have led to reviewer bias. Another limitation is that the review did not look at the interventions given to mothers prenatally, and likewise, interventions that had seen outcome at the age beyond 6 months were not considered in the review.

In spite of these limitations, this review also has some considerable strength. To our knowledge, this is the first review that presents burden and risk factors of acute malnutrition in u6m infants along with the preventive interventions, assessment, and treatment approaches used for u6m infants with acute malnutrition in LICs and LMICs.

The review identified high burden of acute malnutrition in u6m infants in LICs and LMICs which recognizes an urgent need to plan programs and invest resources for management of acute malnutrition in u6m. The review also identified various risk factors associated with acute malnutrition in u6m and knowledge about these factors would help in planning the strategies to prevent growth faltering in infants of this age group. Evidence from this review could be helpful in strategizing community-based support of breastfeeding mothers as a treatment option for uncomplicated cases (without oedema and danger signs) of malnutrition in infants u6m.

Routine immunization visits shortly after birth could be utilized as an effective platform for anthropometric assessment of u6m infants to identify wasted infants at a higher risk of death and thus targeted interventions could be planned accordingly. In addition, as mother’s mental health is found to impact infant’s health, training of community/ frontline health workers could be considered for early screening and identification of depression symptoms in mothers. Detecting and treating maternal depression and child malnutrition simultaneously could be an effective approach and programs can integrate a psychosocial component into existing maternal and child health interventions.

Of all the 33 included studies, only 17 studies had prime focus on u6m infants, while rest were studies that had a component of sub-group analysis in u6m infants. Majority of the studies that reported prevalence and risk factors had SDA as study design. Thus, considerable gap was observed in context specific primary studies with a focus on u6m infants.

The number of studies that measured the impact of preventive interventions on anthropometry and morbidity outcome was very limited, as most of the studies focus only on measuring the improvement in breastfeeding practices.

The review also found that the number of studies focusing on assessment and treatment aspect were very limited. In future studies presenting evidence on the feasibility and accuracy of using MUAC to identifyu6m infants at higher risk of mortality is required. Also, research to identify effective choice of therapeutic milk for infants u6m and follow-up of malnourished non-breastfed infants.

Studies exploring psychosocial support activities to manage depression in pregnant and lactating women and its effects on improving infant’s nutritional status, require urgent consideration.

The review systematically synthesized evidence on burden, risk factors, different preventive interventions in practice, assessment and treatment strategies to manage acute malnutrition in infants u6m from LICs and LMICs. Burden of acute malnutrition in u6m infants in LICs and LMICs is very high, especially in South Asia region. Risk factors identified in the review were mainly maternal related and MNS component along with BF support is identified as an effective strategy to prevent growth faltering in u6m infants. The review also identified that there is paucity in current evidence on assessment and management of acute malnutrition in u6m infants.

In addition, further research on context specific burden of acute malnutrition and identification of underlying risk factors, can help shaping new programs and/ or in incorporating u6m in existing malnutrition management strategies.

We would like to acknowledge the team of Eppi Reviewer and EndNote for their support.